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Maria Dall’Era, MD: Evaluating the Complexities of SRI-4 and BICLA Endpoints in SLE Trials

Dall'Era notes that it is important for rheumatologists to understand that the current endpoints for SLE clinical trials, such as SRI-4 and BICLA, are complex and imperfect. 

Rheumatology Network interviewed Maria Dall’Era, MD, to discuss her study “SRI-4 and BICLA: How Well Do They Agree Across Trials of Active Systemic Lupus Erythematosus?” The trial evaluated the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA), the most common primary endpoints in systemic lupus erythematosus (SLE) trials. Dall’Era is a Jean S. Engleman Distinguished Professor and Chief of the Division of Rheumatology at University of California San Francisco (UCSF), Director of the UCSF Lupus Clinic and the Rheumatology Clinical Research Center, and chair of the Lupus Research Alliance’s (LRA’s) affiliate Lupus Therapeutics' Lupus Clinical Investigators Network.

Data was presented at the American College of Rheumatology (ACR) Convergence 2022.

Rheumatology Network: Can you give me a bit of background on the SRI-4 and BICLA and why your team decided to evaluate the differences between the 2?

Maria Dall’Era, MD: The SRI-4 and the BICLA are the 2 most commonly used endpoints in pivotal non-renal SLE clinical trials. These endpoints were designed during the development program of belimumab (SRI-4) and epratuzumab (BICLA). The overarching principle of these global endpoints is that a participant must demonstrate improvement in active organ domains at baseline without showing worsening in other organ domains. Discordance between the SRI-4 and the BICLA have been observed in several large-scale SLE trials, most recently in the anifrolumab TUILP trials. With that background, our group decided to study the performance of these endpoints with the goal of better understanding how best to use these endpoints in SLE trials.

RN: What were the methods your team used the analysis?

MD: To conduct this study, we analyzed data from the placebo groups from 6 large-scale, industry sponsored non-renal phase 2 or phase 3 SLE clinical trials of either 24- or 52-weeks duration. Participants were classified as SRI-4 or BICLA responder or non-responder, and Cohen’s kappa was used to estimate agreement between the SRI-4 and BICLA. We then identified the reasons for nonresponse.

RN: Do SRI-4 and BICLA ultimately agree across trials regarding active SLE patients?

MD: Discordance between SRI-4 and BICLA varied from 11.8-30.3% and the Cohen’s kappa ranged from 0.39-0.76. Concordance between the measures was higher at 52 weeks than 24 weeks. When discordant, SRI-4 classified more participants as responders than BICLA.

RN: What do rheumatologists need to know about these results?

MD: It is important for rheumatologists to know that current endpoints for SLE clinical trials are complex and imperfect. We are working hard to better understand the performance characteristics of our currently used endpoints (such as SRI-4 and BICLA) while also trying to develop newer endpoints that are better able to measure response to therapies. Rheumatologists will be hearing more about these efforts in the near future.

RN: Is there anything else you’d like our audience to know? 

MD: This study was an example of the successful collaboration between a nonprofit organization (LRA), lupus clinical researchers in academics, and industry scientists. The lupus community is committed to developing new and improved endpoints for SLE trials so that we can successfully develop therapies for people living with lupus.